Abstract
In mammals, the most striking IgA system belongs to Lagomorpha. Indeed, 14 IgA subclasses have been identified in European rabbits, 11 of which are expressed. In contrast, most other mammals have only one IgA, or in the case of hominoids, two IgA subclasses. Characteristic features of the mammalian IgA subclasses are the length and amino acid sequence of their hinge regions, which are often rich in Pro, Ser and Thr residues and may also carry Cys residues. Here, we describe a new IgA that was expressed in New Zealand White domestic rabbits of IGHVa1 allotype. This IgA has an extended hinge region containing an intriguing stretch of nine consecutive Ser residues and no Pro or Thr residues, a motif exclusive to this new rabbit IgA. Considering the amino acid properties, this hinge motif may present some advantage over the common IgA hinge by affording novel functional capabilities. We also sequenced for the first time the IgA14 CH2 and CH3 domains and showed that IgA14 and IgA3 are expressed.
Highlights
The European rabbit (Oryctolagus cuniculus) has the most complex immunoglobulin A (IgA) system observed in mammals, with 13 IGHA genes (Cα) encoding the heavy chain constant regions for 13 IgA subclasses [1]; a fourteenth IGHA was partially described [2]
Understanding how the rabbit mucosal immune system has adapted to this large number of IgA subclasses may open new therapeutic possibilities [30, 31]
In this study we describe the CH2 and CH3 domains of IgA14 as well as an additional IgA being expressed in domestic European rabbits
Summary
The European rabbit (Oryctolagus cuniculus) has the most complex immunoglobulin A (IgA) system observed in mammals, with 13 IGHA genes (Cα) encoding the heavy chain constant regions for 13 IgA subclasses [1]; a fourteenth IGHA was partially described [2]. The Cα3 and Cα8 genes have defective Iα promoter regions and as a result are not expressed in vivo [4] This complex system is even more remarkable and intriguing given that mice [5] and most other mammals have one IGHA gene, coding for one IgA isotype, and hominoid primates (with the exception of orangutan) have two IGHA genes that code for the IgA1 and IgA2 subclasses [6]. These two IGHA genes arose by gene duplication in a common hominoid primate ancestor.
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